Recent reports indicate that a new strain of adenovirus serotype 14 (Ad14) is causing frequent acute respiratory disease (ARD) and deaths in otherwise health people. The overall goal of this SBIR is to generate a vaccine that can protect against Ad14 infection and disease. Our hypothesis is that an Ad14 vector particle that is made non-replicating by means of a deletion in the E1 region, Ad14nr, will be an effective and safe vaccine. Preliminary data supporting this strategy has been obtained. In the phase I portion of this application we will test the feasibility of our strategy by generating an Ad14nr prototype vaccine, testing its yield and quality of production, evaluating immunogenicity and initial testing for safety. In the phase II portion of this SBIR we will conduct IND enabling production and quality testing under Good Manufacturing Practice and complete required safety and biodistribution studies. PUBLIC HEALTH RELEVANCE: Recent reports indicate that a new strain of adenovirus serotype 14 (Ad14) is causing frequent acute respiratory disease (ARD) and deaths in otherwise healthy people. The overall goal of this SBIR is to generate a vaccine that can protect against Ad14 infection and disease.